Bidirectional synaptic plasticity in the rat basolateral amygdala: characterization of an activity-dependent switch sensitive to the presynaptic metabotropic glutamate receptor antagonist 2S-alpha-ethylglutamic acid.
This study examines forms of activity-dependent synaptic plasticity in the basolateral amygdala in vitro and demonstrates that a brief high frequency stimulus (HFS) train can induce a switch in the direction of the enduring change in synaptic strength induced by subsequent low-frequency stimulation (LFS). LFS (1 Hz, 15 min) of the external capsule (EC) induced a persistent 1.7-fold enhancement in the amplitude of synaptic potentials recorded intracellularly in basolateral amygdala neurons. The enhancement occurred gradually during the stimulation and was maintained for >30 min after termination of the stimulus train. LFS-induced enduring synaptic facilitation was not affected by the NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoate (APV; 100 microM). Brief high-frequency EC stimulation (HFS; 100 Hz, 1 sec) induced APV-sensitive short-term potentiation (2.5-fold) that generally decayed within 10 min. When LFS was applied after recovery from the short-term potentiating effect of HFS (HFS/LFS), there was an initial transient (<10 min) enhancement of the synaptic response followed by persistent synaptic depression (synaptic potential amplitude reduced by 22% at 30 min). This represents the first demonstration of stimulus-dependent long-lasting synaptic depression in the amygdala. Application of the presynaptic (group II) metabotropic glutamate receptor antagonist 2S-alpha-ethylglutamic acid (EGLU; 50 microM) prevented the HFS-dependent switch from synaptic facilitation to depression. Thus, LFS in the in vitro amygdala slice can induce either enduring synaptic potentiation or depression, depending on whether a priming HFS train has been applied. This experience-dependent switch, a novel form of metaplasticity, is not dependent on NMDA receptors but may require group II metabotropic glutamate receptors. In the amygdala, experiential modification of activity-dependent long-term synaptic plasticity adds flexibility to the ways in which synaptic strength can be modified and could play a role in diverse amygdala-dependent processes, including the formation, storage, and extinction of emotional memory and the regulation of epileptogenesis.
Li
H
H
Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
Weiss
S R
SR
Chuang
D M
DM
Post
R M
RM
Rogawski
M A
MA
D000679:Amygdala / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D000818:Animals; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000502:physiology; D005971:Glutamates / Q000494:pharmacology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D005971:Glutamates; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C017302:alpha-ethylglutamic acid